Drug Product Development Flashcards
What is preformulation?
Determining the physicochemical properties necessary to formulate the compound
What is formulation?
Determining the route and composition of the final dosage form
What is manufacturing?
The unit operations that are necessary for final dosage preparation
What are the two things to be concerned about for preformulation?
Solubility
Stability
What is solubility?
Equilibrium State
Some leave the surface, some attach to surface and a products solubility is reaching the equilibrium between these.
What is solubility usually described as?
Maximum amount of solute that can be dissolved per 100g of water. it could also be moles of solute per liter of solution.
How are organics solubility?
Low solubility, unless they are salts
What are the 3 states of solubility?
Completely soluble
Supersaturated
Very supersaturated (labile)
Which of the 3 states of solubility results in crystallization?
supersaturation
What are 2 properties of stability?
Physical and Chemical
How does physical stability work?
When it transforms to different crystal forms, but the chemical stays in tact. Eg. crystalline to amorphous, hydrates, solvates
What defines chemical stability?
Chemical reactions.
Results in degradation of product that must be characterized
Why are solids very stable?
The crystal lattice helps to keep molecules from reacting
Is the crystalline form or amorphous form more reactive?
Amorphous
Where do reactions start?
At crystal defects
What are the 5 crystal defects?
Interstitial atom Substitution larger atom Substitution smaller atom Vacancy Frenkel-pair
What does the Prout-Tompkins equation describe?
Reactivity in solids
Are you more concerned with an initial degradation or later degradation in a product?
Initial because later degradation means it was a failed product.
What are 4 reactions that can ruin the stability of your drug?
Hydrolysis
Oxidation
Photolysis
Dehydration
What is the IPEC?
International Pharmaceutical Excipients Council
What is the IPEC definition of an excipient?
Any substance other than the active drug or prodrug which has been appropriately evaluated for safety and is included in a drug delivery system for a specific purpose
What does the USP do?
Provides test procedures and specifications to find the right excipient
What are the 6 types of excipients?
Diluents Disintegrants Binders Lubricants Glidants Controlled release
What is a diluent?
Bulk forming agent
Helps make weight practical for tablet
Helps keep tablet together
Enhances powder flow for manufacturing
What are some examples of diluents?
Microcrystalline cellulose Lactose Calcium phosphate dibasic dihydrate Starch Compressible sugar
What is a disintegrant?
Breaks up solid dosage form, enhancing dissolution
Works by either water uptake and/or swelling
What are some examples of disintegrants?
Sodium starch glycolate
Croscarmellose sodium
Crospovidone
Starch
What is a binder?
Gives tables mechanical strength, creates granules in wet milling
Works by either water uptake and/or swelling
What are some examples of a binder?
Polyvinylpyrrolidone (PVP)
Starch
Microcrystalline cellulose
Polymers
What are lubricants?
Prevents adherence of tablet to the die after compaction
Over lubrication can affect the dissolution
Used at levels of 0.5%-2%
What are some examples of lubricants?
Magnesium stearate
Stearic acid
Lubritab
Talc
What are glidants?
Improves powder flow Stops inter-particle friction Used at levels <0.2% Low bulk density Can have problems with asbestos (with talc)
What are some examples of glidants?
Fumed silica
Talc
What are controlled release/protection?
Used to extend the release of drug from a matrix
What are some examples of controlled release?
HPMC
Xanthan gum
What are some examples of protection?
Eudragits
Won’t dissolve until it reaches a high pH
Where does manufacturing start?
Preformulation
What are two ways to adjust particle sizes and how do they effect the particle?
Milling-decreases
Granulation-increases
Why do we adjust the particle size?
If the particles are different sizes they will not properly mix
What are 4 ways to mill?
Cutting
Compreshion
Impact
Attrition
What is the definition of milling?
Create a stress on particle to cause it to break
What are two examples of milling machines?
Fitz Mill
CoMill
What are two methods of granulation?
Wet granulation
Dry granulation
What are the two processes of wet granulation?
Nucleation
Ball growth
What are 4 types of granulation?
Coalescence
Breakage
Abrasion transfer
Layering
What are two machines used for wet granulation?
High speed mixer/granulator
Fluidized-bed granulator
What are two methods of dry granulation?
Slugging-not as much
Roller compaction
What is the name of a machine for roller compaction
Roller compactor
What press is used for small manufacturing?
Tablet press
What press is used for large manufacturing?
Rotary press
What tests are ran after the tablet has been made?
Tablet thickness Hardness test
